本文關(guān)鍵詞： 子宮內(nèi)膜樣腺癌 子宮內(nèi)膜非典型增生 保留生育功能 輔助生殖技術(shù) 妊娠　出處：《天津醫(yī)科大學(xué)》2017年博士論文　論文類(lèi)型：學(xué)位論文

【摘要】：研究背景和目的:子宮內(nèi)膜癌常見(jiàn)于圍絕經(jīng)期及絕經(jīng)后的女性,近些年來(lái),子宮內(nèi)膜癌的發(fā)病率呈現(xiàn)逐年上升并且顯現(xiàn)出年輕化的趨勢(shì),40歲以下的患者所占比例上升可以達(dá)到14%,其中年齡小于40歲的患者中有約80%以上的患者未曾生育或者仍然有再生育的愿望。因此嘗試保留年輕并且有生育要求的子宮內(nèi)膜癌患者的生育功能,是目前婦科臨床和生殖醫(yī)學(xué)領(lǐng)域的熱點(diǎn)問(wèn)題。由于子宮內(nèi)膜癌常常較早出現(xiàn)臨床癥狀,被診斷時(shí)多數(shù)處于疾病早期,預(yù)后相對(duì)較好,并且多數(shù)病例對(duì)激素治療敏感,這為年輕的子宮內(nèi)膜癌患者進(jìn)行保留生育功能的治療提供了依據(jù)。子宮內(nèi)膜癌保留生育功能的治療目前仍缺乏大樣本的隨機(jī)對(duì)照臨床試驗(yàn),2012年NCC N指南首次提到年輕子宮內(nèi)膜癌患者保留生育功能治療,直到2016年NCCN指南仍只是建議年輕子宮內(nèi)膜癌保留生育功能的治療的適應(yīng)癥,在治療的諸多方面尚未取得共識(shí),如孕激素治療的用量、治療時(shí)間、治療后的后續(xù)治療及隨訪(fǎng)仍未明確,目前尚沒(méi)有預(yù)測(cè)孕激素治療效果的相關(guān)分子指標(biāo)。本研究采用前瞻性的研究方法,采用大劑量口服孕激素為主同時(shí)配合口服二甲雙胍、他莫昔芬及宮腔鏡下子宮內(nèi)膜病灶切除術(shù)治療早期子宮內(nèi)膜癌及子宮內(nèi)膜非典型增生的患者,對(duì)符合納入標(biāo)準(zhǔn)的就診于天津市中心婦產(chǎn)科醫(yī)院的早期子宮內(nèi)膜癌及子宮內(nèi)膜非典型增生患者共36例進(jìn)行調(diào)查分析,總結(jié)臨床資料,分析治療效果、妊娠結(jié)局、生存結(jié)局及相關(guān)影響因素。本研究的目的在于進(jìn)一步驗(yàn)證早期子宮內(nèi)膜癌及子宮內(nèi)膜非典型增生患者保留生育功能治療的安全性及有效性,并嘗試為預(yù)測(cè)影響妊娠率的相關(guān)因素提供參考指標(biāo)。研究對(duì)象和方法::研究對(duì)象的入選標(biāo)準(zhǔn):(1)年齡≤40歲并有強(qiáng)烈的保留生育功能的愿望及要求;(2)組織病理學(xué)診斷為高分化子宮內(nèi)膜樣腺癌或子宮內(nèi)膜非典型增生;(3)免疫組織化學(xué)染色測(cè)定孕激素受體陽(yáng)性。(4)無(wú)血清CA125的升高;(5)經(jīng)陰道彩色多普勒超聲檢查(T VS)和/或核磁共振(MRI)檢查未發(fā)現(xiàn)有肌層浸潤(rùn)以及宮頸實(shí)質(zhì)的受累,未發(fā)現(xiàn)子宮外轉(zhuǎn)移的證據(jù);(6)無(wú)應(yīng)用相關(guān)藥物的禁忌癥;(7)具備密切隨訪(fǎng)的條件,依從性良好;(8)理解保留生育功能治療的利弊,強(qiáng)烈要求進(jìn)行保留生育功能的治療并簽署知情選擇同意書(shū)。研究方法:所有患者保守治療前均行宮腔鏡檢查+全面清宮術(shù),既能達(dá)到明確診斷又能減少腫瘤負(fù)荷的目的。從月經(jīng)或?qū)m腔鏡檢查診刮后的第五天開(kāi)始周期性(21天)口服醋酸甲地孕酮(MA)160 mg/天,停藥來(lái)月經(jīng)后第五天再開(kāi)始下一周期的治療,停藥2周不來(lái)月經(jīng)者為避免無(wú)治療間隔的延長(zhǎng),則改為連續(xù)性口服醋酸甲地孕酮160 mg/天治療,免疫組化測(cè)定孕激素受體(P R)指數(shù)低于50%者加枸櫞酸他莫昔芬20 mg/天口服,治療前有糖尿病或胰島素抵抗者加二甲雙胍750 mg/天口服。治療過(guò)程中如T VS或MRI檢查提示有宮腔占位性病變,則行宮腔鏡下子宮內(nèi)膜病灶電切術(shù),術(shù)后再繼續(xù)口服M A160 mg/日治療。每3個(gè)周期治療后行宮腔鏡檢查及全面診刮術(shù)獲得子宮內(nèi)膜組織送病理檢查評(píng)估子宮內(nèi)膜的變化。子宮內(nèi)膜獲得病理完全緩解后即轉(zhuǎn)入輔助生殖中心助孕,爭(zhēng)取早日妊娠。結(jié)果:研究共納入17例子宮內(nèi)膜樣腺癌(E C)和19例子宮內(nèi)膜非典型增生(AE H)患者,中位年齡31歲。大劑量口服孕激素為主的保守治療有31例患者(86.1%)獲得完全反應(yīng)(CR),2例患者(5.6%)獲得部分反應(yīng)(PR),2例患者(5.6%)病情穩(wěn)定(SD),1例患者(2.8%)疾病進(jìn)展(PD)。獲得病理完全反應(yīng)的平均時(shí)間為8.26±0.87個(gè)月。其中有1例患者因發(fā)生嚴(yán)重不良反應(yīng)(雙下肢靜脈血栓)而終止治療,最終因并發(fā)腹膜癌而行手術(shù)治療。平均隨訪(fǎng)26.17±2.60個(gè)月,復(fù)發(fā)率為19.4%(6/31),平均復(fù)發(fā)時(shí)間為29.5±5.64個(gè)月,6例復(fù)發(fā)患者中2例患者接受手術(shù)治療,4例患者再次進(jìn)行保留生育功能治療,其中2例患者獲得病理完全反應(yīng),2例患者仍在保守治療中。截至最后一次隨訪(fǎng)全部保守治療的患者有32例患者無(wú)疾病生存,4例患者帶病存活。進(jìn)行保留生育功能治療后子宮內(nèi)膜病理獲得完全反應(yīng)并且有迫切生育愿望的患者共25例,9例患者妊娠11次,妊娠率為36%,獲得活產(chǎn)兒4名,生育率為16%。從停止保守治療到獲得妊娠的時(shí)間平均為7.33±0.83個(gè)月。結(jié)論:本課題采用前瞻性的研究方法,應(yīng)用口服大劑量孕激素為主配合口服二甲雙胍、他莫昔芬及宮腔鏡下子宮內(nèi)膜病灶切除術(shù)保留生育功能治療早期子宮內(nèi)膜癌和子宮內(nèi)膜非典型增生的患者,多種方式聯(lián)合保守治療的方案國(guó)內(nèi)外報(bào)道少見(jiàn)。獲得了較滿(mǎn)意的逆轉(zhuǎn)率和一定的妊娠率,86.1%獲得完全反應(yīng),36%妊娠,人工輔助生殖技術(shù)顯著提高了妊娠率。1 9.4%的患者出現(xiàn)復(fù)發(fā),全部患者32例無(wú)疾病生存,4例帶病存活。
[Abstract]:Background and objective: endometrial cancer is common in perimenopausal and postmenopausal women, in recent years, the incidence of endometrial cancer has been rising and showing the trend of younger patients under the age of 40, the proportion reached 14%, of which less than 40 years of age with more than about 80% patients not birth or still have fertility desire. So try to keep young and endometrial cancer patients with fertility requirements of reproductive function, is a hot issue in clinical gynecology and reproductive medicine at present. Due to endometrial cancer often appears early clinical symptoms, was diagnosed at most in the early stage of the disease, the prognosis is relatively good, and most a case sensitive to hormone therapy, which provides a basis for endometrial carcinoma in young patients with the fertility sparing treatment. The treatment of endometrial cancer with reproductive function preserved There is still a lack of randomized controlled clinical trials of large sample, the 2012 NCC N guide was first mentioned in the young patients with endometrial carcinoma fertility preserving treatment, treatment until the 2016 NCCN guidelines still recommend young endometrial cancer to preserve fertility indications, no consensus in many aspects of treatment, such as the dosage of progestin therapy, treatment time, follow-up treatment and follow-up after treatment is not clear, there is no related molecular markers to predict the effect of progesterone treatment. This study used a prospective research method, with large doses of oral progesterone hormone mainly with oral metformin, tamoxifen and hysteroscopic endometrial resection in treatment of patients with early endometrial cancer and endometrial atypical hyperplasia, met the inclusion criteria from Tianjin Central Obstetrics and Gynecology Hospital during early endometrial cancer and Endometrial atypical hyperplasia patients with a total of 36 cases were investigated and analyzed, summarized the clinical data, analysis of the treatment effect, pregnancy outcome and related factors of survival outcomes. The purpose of this study is to further verify the early endometrial cancer and endometrial atypical hyperplasia patients with preserved fertility safety and effectiveness of treatment, and try to predict the impact of related factors of pregnancy rate and provide reference index. The research object and methods: the inclusion criteria: (1) the desire and requirement of older than 40 years of age and have strong reproductive function preserved; (2) the histopathological diagnosis was well differentiated endometrioid adenocarcinoma or atypical endometrial hyperplasia (3); Determination of progesterone receptor positive immunohistochemical staining. (4) elevated serum free CA125; (5) transvaginal color Doppler ultrasound (T VS) and / or nuclear magnetic resonance (MRI) examination found no myometrial invasion and The essence of cervical involvement, no evidence is found outside the uterus transfer; (6) no contraindications to application related drugs; (7) with close follow-up, good compliance; (8) to understand the advantages and disadvantages of fertility treatment, strong demand for fertility sparing treatment and signed informed consent. The method of selection conservative treatment all patients underwent hysteroscopy and curettage can achieve comprehensive, clear diagnosis and reduce the tumor burden. Starting from menstrual periodic or hysteroscopy curettage after fifth days (21 days) oral megestrol acetate (MA) mg/ 160 days, fifth days after stopping menstruation before the start of the next cycle of treatment, drug withdrawal for 2 weeks to avoid prolonged menstruation does not come without the treatment interval, instead of continuous oral megestrol acetate 160 mg/ days of treatment, immunohistochemical determination of progesterone receptor (P R) index of less than 50% with citric acid Tamoxifen 20 mg/ day orally, have diabetes or insulin resistance plus metformin 750 mg/ day oral before treatment. The treatment process such as T VS or MRI examinations showed uterine cavity lesions, underwent hysteroscopic endometrial lesion resection, M A160 mg/, and then continue to oral therapy after operation. 3 cycle treatment by hysteroscopy and curettage was full of endometrial tissue for pathological examination to assess the changes of the uterine endometrium. Endometrial pathological complete remission after moving into the center of assisted reproduction pregnancy, early pregnancy. Results: there were 17 cases of endometrioid adenocarcinoma (E C) and 19 cases of endometrial atypical hyperplasia (AE H) with a median age of 31 years. Large dose of oral progesterone conservative treatment of 31 patients (86.1%) achieved a complete response (CR), 2 patients (5.6%) received partial response (PR), 2 patients stable disease (SD (5.6%) ), 1 patients (2.8%) disease progression (PD). The average time of pathological complete response was 8.26 + 0.87 months. There were 1 patients due to serious adverse reaction (deep vein thrombosis) and eventually discontinued treatment due to complicated peritoneal carcinoma treated surgically. The average follow-up was 26.17 + 2.60 months and the recurrence rate was 19.4% (6/31), the average recurrence time was 29.5 + 5.64 months, 6 cases of recurrence in 2 patients who underwent surgical treatment, 4 patients again fertility preserving treatment, including 2 cases of patients with pathological complete response, 2 patients were still in the conservative treatment at the end of follow-up. All the patients were treated conservatively and 32 cases were disease-free survival, 4 patients living with the disease. To preserve fertility after treatment of endometrial pathology obtained complete response and there is an urgent desire to procreate with a total of 25 cases, 9 patients with 11 pregnancies, the pregnancy rate was 36%, achieved live Children 4, the fertility rate is obtained from the 16%. to stop pregnancy conservative treatment for an average of 7.33 + 0.83 months. Conclusion: this topic using prospective research method, the application of high-dose oral progesterone combined with oral metformin, tamoxifen and hysteroscopic endometrial resection to preserve the fertility of the treatment of early endometrial cancer and endometrial atypical hyperplasia patients, the combination of various methods of conservative treatment scheme is rarely reported at home and abroad. The reversal rate is satisfactory and the pregnancy rate was 86.1%, achieved a complete response, 36% pregnancy, assisted reproductive technology can significantly improve the pregnancy rate of 9.4% patients with.1 recurrence, all 32 patients with disease-free survival. 4 patients living with the disease.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R737.33

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 單波兒;任玉蘭;孫建民;涂小予;蔣朝霞;居杏珠;臧榮余;王華英;;年輕早期高分化子宮內(nèi)膜樣腺癌或子宮內(nèi)膜不典型增生保留生育功能的Ⅱ期臨床研究[J];中國(guó)癌癥雜志;2012年06期

2 王剛;;子宮內(nèi)膜癌保留生育功能治療的研究與應(yīng)用[J];實(shí)用婦產(chǎn)科雜志;2008年09期

3 王剛;林鐵成;謝詠;梁棟;陳汝芳;鄭麗麗;吳浩泉;;子宮內(nèi)膜癌保留生育功能治療的臨床探討[J];中國(guó)實(shí)用婦科與產(chǎn)科雜志;2008年02期

相關(guān)博士學(xué)位論文 前1條

1 曹冬焱;早期子宮內(nèi)膜癌及重度不典型增生患者保留生育功能治療的臨床和基礎(chǔ)研究[D];北京協(xié)和醫(yī)學(xué)院;2011年

，

本文編號(hào)：1495522